In our study, sentinel signals EGR-1 and ERK1/2 MAP kinase were proposed for their involvement in the pro-inflammatory interleukin-8 gene
JTP74057 in the intestinal epithelial cells. Although there is no EGR-1 binding motif in promoter of interleukin-8 gene, EGR-1-associated IL-8 production could be investigated in combination with three central transcription factors such as NF-κB, C/EBP, or AP-1 since these transcription factors also partly contribute to DON-mediated IL-8 transcriptional activation. The expression of EGR-1 can be induced by a range of stimuli, which in many cases overlap with those known to be capable of inducing NF-κB expression [26], [27] and [28]. NF-κB and EGR-1 have been shown to cooperatively stimulate IL-8 gene transcription promoter [29] despite of a report that Egr-1 specifically represses NF-κB transcriptional activity in a regulatory way by preventing its interaction with
promoter target elements [30]. In addition, it has been studied that AP-1 is the positive downstream of EGR-1 in a cooperative way [31]. Therefore, we can speculate the cooperation between EGR-1 and other transcription factors can promote IL-8 transcription although the individual major cis-acting elements showed partial contribution to DON-induced IL-8 expression. However, the positive association between EGR-1 and IL-8 could be from another indirect communication in the human epithelium. It is thus warranted as a further study that another modulating mechanism by EGR-1 can contribute to the DON-induced IL-8 transcription.
